ArticleJournal of basic and clinical physiology and pharmacology2016
CB1 cannabinoid receptor-mediated increases in cyclic AMP accumulation are correlated with reduced Gi/o function.
Article in Journal of basic and clinical physiology and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Side-Chain Homologs of ΔMolecular neurobiology · 2026Article
- Transcriptional Mapping of the Human Cannabinoid Receptor 1 (Molecules (Basel, Switzerland) · 2026Article
- Inhibition of endocannabinoid degradation in astrocytes reprograms glial reactivity and prevents seizure sequelae.Journal of neuroinflammation · 2026Article
- Canonical Cannabinoid Receptors.Current topics in behavioral neurosciences · 2026Review
- Real-Time Optical Control of CB1 Receptor SignalingJournal of the American Chemical Society · 2025Article
- Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery.Acta pharmacologica Sinica · 2025Review
- Cannabinoid Receptors Reduced Early Brain Damage by Regulating NOX-2 and the NLRP3 Inflammasome in an Animal Model of Intracerebral Hemorrhage.CNS neuroscience & therapeutics · 2025Article
- CB1 receptor coupling to extracellular regulated kinase via multiple Gαi/o isoforms.Neuroreport · 2025Article
- Decoding the Therapeutic Potential of Cannabis and Cannabinoids in Neurological Disorders.Current pharmaceutical design · 2025Review
- Pharmacological Characterization of the Endocannabinoid Sensor GRABCannabis and cannabinoid research · 2024Article
- P2XBritish journal of pharmacology · 2024Article
- The NPXXY Motif Regulates β-Arrestin Recruitment by the CB1 Cannabinoid Receptor.Cannabis and cannabinoid research · 2023Article
- Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity.Biomedicines · 2023Review
- Activation of CB1R alleviates central sensitization by regulating HCN2-pNR2B signaling in a chronic migraine rat model.The journal of headache and pain · 2023Article
- Article
- Exploring determinants of agonist efficacy at the CB1 cannabinoid receptor: Analogues of the synthetic cannabinoid receptor agonist EG-018.Pharmacology research & perspectives · 2022Article
- Axonal CB1 Receptors Mediate Inhibitory Bouton Formation via cAMP Increase and PKA.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- CB1 Cannabinoid Receptor Signaling and Biased Signaling.Molecules (Basel, Switzerland) · 2021Review
- A proposed modulatory role of the endocannabinoid system on adipose tissue metabolism and appetite in periparturient dairy cows.Journal of animal science and biotechnology · 2021Review
- Optimization of the Heterologous Expression of the Cannabinoid Type-1 (CBFrontiers in endocrinology · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCB1 cannabinoid receptors (CB1Rs) stimulate Gi/o-dependent signaling pathways. CB1R-mediated cAMP increases were proposed to result from Gs activation, but CB1R-stimulated GTPγS binding to Gs has not heretofore been investigated.
methodsThree models of CB1R-stimulated cAMP production were tested: pertussis toxin disruption of Gi/o in N18TG2 cells; L341A/A342L-CB1R expressed in Chinese hamster ovary (CHO) cells; and CB1 and D2 dopamine receptors endogenously co-expressed in MN9D cells. cAMP was assayed by [3H]cAMP binding competition. G protein activation was assayed by the antibody-targeted scintillation proximity assay.
resultsIn L341A/A342L-CB1-CHO cells, cannabinoid agonists significantly stimulated cAMP accumulation over vehicle; (-)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)phenyl]-4-[3-hydroxyl propyl] cyclohexan-1-ol (CP55940)-stimulated [35S]GTPγS binding to Gi1/2/3 was reversed, whereas binding to Gs was not different from CB1R. In MN9D cells, CB1 agonist HU210 or D2 agonist quinpirole alone inhibited forskolin-activated cAMP accumulation, whereas HU210 plus quinpirole increased cAMP accumulation above basal. HU210 alone stimulated [35S]GTPγS binding to Gi1/2/3, whereas co-stimulation with quinpirole reversed HU210-stimulated [35S]GTPγS binding to Gi1/2/3.
conclusionsCB1R couples to Gs but with low efficacy compared to Gi/o. The L341A/A342L mutation in CB1R reversed CP55940 activation of Gi to an inhibition, but had no effect on Gs. Combined CB1 plus D2 agonists in MN9D cells converted the CB1 agonist-mediated activation of Gi to inhibition of Gi. In these models, the CB1 agonist response was converted to an inverse agonist response at Gi activation. Cannabinoid agonist-stimulated cAMP accumulation can be best explained as reduced activation of Gi, thereby attenuating the tonic inhibitory influence of Gi on the major isoforms of adenylyl cyclase.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.